The Human Immunodeficiency Virus (HIV) infects cells of the immune system, especially those bearing the CD4 membrane receptor (largely T-helper cells and a certain percentage of circulating monocytes) 1!. With time, individuals exhibit a degree of immunosuppression due to the constant loss of their CD4 cells but also largely due to the functional dysregulation of these cells (proliferation in response to antigens, cytotoxic acitivity and secretion of immunoregulatory cytokines) 2,3!. It has also been shown that disease progression is paralleled by overt autoimmune processes (thrombocytopaenia, lymphopaenia, arthritis, etc.) 4!. The loss of immune cells has been partly attributed to the increased frequency of apoptosis (programmed cell death) which is evident in the peripheral blood of HIV infected individuals 5,6!. Also of note is the fact that several reports have shown increased levels of the pro-inflammatory cytokines IL6 and TNF-.alpha. in the sera of infected persons 7,8! and it had been shown that these cytokines are capable of activating viral replication in latently infected cells.
The Feline Immunodeficiency Virus (FIV), the feline counterpart of HIV, infects immune cells of cats and induces an equivalent pathology to that induced by the HIV 9!. Indeed, the cats thus infected demonstrate immunosuppression with time (due to quantitative and qualitative CD4 cell loss and dysregulation) and finally succumb to death due to opportunistic infections. An interesting phenomenon described, is the secondary infertility associated with FIV infection. Many authors have argued that due to the similarities between HIV and FIV pathologies, the feline virus can be used as a model to study the outcome of therapies before these are attempted in human subjects.
The Applicant has previously shown (U.S. Pat. No. 5,486,510; EPO Patent Application 92302556.3) that BSS and BSSG either on their own or preferably in a mixtrue (ratio of BSS to BSSG between 1:1 and 500:1) are capable of modulating the immune response of T cells as well as NK cells in vitro and in vivo. Indeed, the Applicant has shown that T cells are capable of increasing their proliferative responses to mitogens and enhancing their secretion of lymphokines such as IL2 and Gamma Interferon when in the presence of the BSS:BSSG mixture. In parallel, NK cells exhibit enhanced lytic activity against cancer cells when co-cultured with the BSS:BSSG mixture 10!.
No claim was made in U.S. Pat. No. 5,486,510 or EPO 92302556 for the treatment of HIV positive patients because the increased T cell proliferation observed on treatment with a BSS:BSSG mixture suggested a favorable environment for HIV replication since T cells and monocytes (under the influence of monokines such as IL6 and TNF.alpha.) are used by the HIV for its replicative cycles. Treatment of HIV infections and the accompanying AIDS symptoms were therefore specifically excluded from any claims made in U.S. Pat. No. 5,486,510 and its equivalent patent applications. Nevertheless, in vitro and in vivo investigations were continued to investigate the validity of this assumption. Surprising and unexpected results obtained to date have now indicated an exciting possibility of the stabilization of CD4 cell numbers (a special T cell type preferentially infected by the HIV or FIV in humans or cats respectively) over an extended time period on treatment with BSS and BSSG mixtures with concomitant decrease in viral load, a decrease in apoptotic lymphocytes in the circulation of HIV positive patients and a significant decrease in the levels of the pro-inflammatory monokine responsible for HIV replication, namely IL6.
In this specification, the term HIV will be used to include the term FIV as well, unless otherwise specifically distinguished.